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TitleStructure of a Pancreatic ATP-Sensitive Potassium Channel.
Journal, issue, pagesCell, Vol. 168, Issue 1-2, Page 101-110.e10, Year 2017
Publish dateJan 12, 2017
AuthorsNingning Li / Jing-Xiang Wu / Dian Ding / Jiaxuan Cheng / Ning Gao / Lei Chen /
PubMed AbstractATP-sensitive potassium channels (K) couple intracellular ATP levels with membrane excitability. These channels play crucial roles in many essential physiological processes and have been implicated ...ATP-sensitive potassium channels (K) couple intracellular ATP levels with membrane excitability. These channels play crucial roles in many essential physiological processes and have been implicated extensively in a spectrum of metabolic diseases and disorders. To gain insight into the mechanism of K, we elucidated the structure of a hetero-octameric pancreatic K channel in complex with a non-competitive inhibitor glibenclamide by single-particle cryoelectron microscopy to 5.6-Å resolution. The structure shows that four SUR1 regulatory subunits locate peripherally and dock onto the central Kir6.2 channel tetramer through the SUR1 TMD0-L0 fragment. Glibenclamide-bound SUR1 uses TMD0-L0 fragment to stabilize Kir6.2 channel in a closed conformation. In another structural population, a putative co-purified phosphatidylinositol 4,5-bisphosphate (PIP) molecule uncouples Kir6.2 from glibenclamide-bound SUR1. These structural observations suggest a molecular mechanism for K regulation by anti-diabetic sulfonylurea drugs, intracellular adenosine nucleotide concentrations, and PIP lipid.
External linksCell / PubMed:28086082
MethodsEM (single particle)
Resolution5.6 Å
Structure data

EMDB-6689, PDB-5wua:
Structure of a Pancreatic ATP-sensitive Potassium Channel
Method: EM (single particle) / Resolution: 5.6 Å

Source
  • mus musculus (house mouse)
  • synthetic construct (others)
  • mesocricetus auratus (golden hamster)
KeywordsATP Binding Cassette Transporter, Subfamily B / Animals / Cryoelectron Microscopy / Humans / Hydrolases / KATP Channels / Kir6.2 channel / Mammals / Mesocricetus / Mice / Models, Molecular / Phosphoinositide Phospholipase C / Potassium Channels, Inwardly Rectifying / Sulfonylurea Receptors / TRANSPORT PROTEIN / KATP / channel / ABC transporter / Kir

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